Visualisation of serotonin-1A (5-HT1A) receptors in the central nervous system

The 5-HT1A subtype of receptors for the neurotransmitter serotonin is predo minantly located in the limbic forebrain and is involved in the modulation of emotion and the function of the hypothalamus. Since 5-HT1A receptors are implicated in the pathogenesis of anxiety, depression, hallucinogenic beha viour, motion sickness and eating disorders, they are an important target f or drug therapy. Here, we review the radioligands which are available for v isualisation and quantification of this important neuroreceptor in the huma n brain, using positron emission tomography (PET) or single-photon emission tomography (SPET). More than 20 compounds have been labelled with carbon-1 1 (half-life 20 min), fluorine-18 (half-life 109.8 min) or iodine-123 (half -life 13.2 h): structural analogues of the agonist, 8-OH-DPAT, structural a nalogues of the antagonist, WAY 100635, and apomorphines. The most successf ul radioligands thus far are [carbonyl-C-11] WAY-100635 (WAY), [carbonyl-C- 11]desmethyl-WAY-100635 (DWAY), p-[F-18]MPPF and [C-11]robalzotan (NAD-299) . The high-affinity ligands WAY and DWAY produce excellent images of 5-HT1A receptor distribution in the brain (even the raphe nuclei are visualised), but they cannot be distributed to remote facilities and they probably cann ot be used to measure changes in endogenous serotonin. Binding of the moder ate-affinity ligands MPPF and NAD-299 may be more sensitive to serotonin co mpetition and MPPF can be distributed to PET centres within a flying distan ce of a few hours. Future research should be directed towards: (a) improvem ent of the metabolic stability in primates; (b) development of a fluorinate d radioligand which can be produced in large quantities and (c) production of a radioiodinated or technetium-labelled ligand for SPET.